Downregulation of miR-181c-5p in Alzheimer's disease weakens the response of microglia to Aβ phagocytosis.

Alzheimer's disease (AD) is an age-associated neurodegenerative disease. Recently, studies have demonstrated the potential involvement of microRNA-181c-5p (miR-181c-5p) in AD. However, the mechanism through which miR-181c-5p is responsible for the onset and progression of this disease remains unclear, and our study aimed to explore this problem. Differential expression analysis of the AD dataset was performed to identify dysregulated genes. Based on hypergeometric analysis, AD differential the upstream regulation genes miR-181c-5p was found. We constructed a model where SH-SY5Y and BV2 cells were exposed to Aβ1-42 to simulate AD. Levels of tumor necrosis factor-alpha, interleukin-6, and IL-1β were determined using enzyme-linked immunosorbent assay or reverse transcription quantitative polymerase chain reaction. Phosphorylation levels of p-P38 and P38 were detected by Western blot. The level of apoptosis in BV2 cells under Aβ1-42 stress was exacerbated by miR-181c-5p mimic. Downregulated miR-181c-5p impaired the phagocytosis and degradation of Aβ by BV2 cells. The release of proinflammatory cytokines in BV2 cells with Aβ1-42 stress was alleviated by miR-181c-5p upregulation. Additionally, miR-181c-5p downregulation alleviated the phosphorylation of P38 in Aβ1-42-induced SH-SY5Y cells. In conclusion, miR-181c-5p improves the phagocytosis of Aβ by microglial cells in AD patients, thereby reducing neuroinflammation.